Application of 3-bromopyruvic acid in preparation of drug for treating pulmonary arterial hypertension

A technology of pulmonary hypertension and bromopyruvate, which is applied in drug combinations, active ingredients of anhydride/acid/halide, cardiovascular system diseases, etc., can solve problems such as poor efficacy, reduce pulmonary vascular remodeling, and increase cardiac output The effect of promoting apoptosis

CN106727473AInactive Publication Date: 2017-05-31张锐
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Authority / Receiving Office
CN · China
Current Assignee / Owner
Publication Date
2017-05-31
Estimated Expiration
Not applicable · inactive patent

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Abstract

The invention belongs to the pharmaceutical chemistry field and provides application of 3-bromopyruvic acid in preparation of a drug for treating pulmonary arterial hypertension. Experiments prove that 3-bromopyruvic acid is capable of effectively decreasing average pulmonary arterial pressure and pulmonary vascular resistance of mice with the pulmonary arterial hypertension, increasing cardiac output, inhibiting the abnormal proliferation of pulmonary arterial smooth muscle cells and promoting the apoptosis and remarkably relieving pulmonary vascular remodeling, and the pulmonary arterial hypertension can be treated by inhibiting the expression of hexokinase.
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Description

[0001] Technical field:

[0002] The invention belongs to the field of medicinal chemistry, and relates to a chemical medicine 3-bromopyruvate, specifically the application of 3-bromopyruvate in preparing medicine for treating pulmonary hypertension.

[0003] Background technique:

[0004] 3-Bromopyruvate is an alkylating agent, which is an analog of cell metabolites pyruvate and lactic acid, which can act on the glycolytic pathway and bind to the -XH group of the active site of hexokinase (HK-2) ( EXH+BrCH 2 -CO-COOH→EX-CH 2 -CO-COOH+HBr) inhibits the activity of the enzyme, which can effectively reduce the production of ATP in cells. 3-Bromopyruvate is very similar to lactic acid in terms of chemical properties and structure, and lactic acid is the final product of glucose after glycolytic metabolism, which allows 3-bromopyruvate to enter and exit cells through the same carrier as lactic acid, thereby exerting Antitumor effect. 3-Bromopyruvate has high efficiency and low ...

Examples

Embodiment 1

[0016] 1. Materials and methods

[0017] 1.1 Establishment of Rat Pulmonary Hypertension Model

[0018] Male SPF grade SD rats (provided by the animal room of Shanghai Chinese Academy of Sciences), weighing 200-220g. One-time subcutaneous injection of monocrotaline (Monocrotaline, MCT, 60mg / kg), 3 weeks later, right heart catheterization was used randomly to measure pulmonary artery pressure and hemodynamic parameters to identify whether the model was successfully established.

[0019] 1.2 Experimental grouping and drug intervention

[0020] (1) Model group (MCT group): 10 rats were given normal saline by intragastric administration after the pulmonary hypertension model was successfully established for 3 consecutive weeks.

[0021] (2) 3-bromopyruvate low-dose group (3-BrPA 15mg·kg·d group): 10 rats were given Tongxinluo by intragastric administration after the successful establishment of the pulmonary arterial hypertension model for 3 consecutive weeks.

[0022] (3) 3-bro...